Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Control mechanisms of normal differentiation are disrupted in cancer cells but can be restored by treatment with site-selective cAMP analogs. The cellular events associated with such changes entail compartmental redistribution of the cAMP-dependent protein kinase type II regulatory subunit, RII beta. The results of this study indicate that the molecular mechanisms of action involve changes in specific DNA-binding activity of putative transcription factors. Gel retardation analyses revealed that nuclear extracts from cells of various human cancer cell lines [colon cancer (LS-174T), gastric cancer (TMK-1), and leukemia (K-562)] and rodent pheochromocytoma (PC12) show a concentration-dependent increase in binding activity to a synthetic DNA that contained the cAMP-responsive element 5'-TGACGTCA-3' after treatment with 8-Cl-cAMP. Such an increase in cAMP-responsive element binding activity was not observed in the 8-C1-cAMP-unresponsive MKN-1 gastric cancer cells. These findings indicate that the antitumor activity of site-selective cAMP analogs may reside in the induction of transcription factors that restore normal gene regulation in cancer cells.
 ...
PMID:Site-selective 8-Cl-cAMP which causes growth inhibition and differentiation increases DNA (CRE)-binding activity in cancer cells. 252 74

Distributions and activities of both cyclic adenosine 3',5'-monophosphate phosphodiesterase and cyclic guanosine 3',5'-monophosphate phosphodiesterase (cAMP-PDE and cGMP-PDE) in 43 human stomach cancer tissues were studied histochemically. The relationship between cyclic nucleotide phosphodiesterases and some patho-biologic behaviors of stomach cancer was preliminarily discussed, and so was the application of these two enzymes in clinical practice of gastric cancers. The Results showed that the two cyclic nucleotide phosphodiesterases were closely correlated with some patho-biologic behaviors of stomach cancer. The authors considered that the histochemical investigation of cyclic nucleotide phosphodiesterases in stomach cancer tissues can be useful in determining the malignant degree and estimating the prognosis of stomach cancer objectively.
 ...
PMID:[Relationship between cyclic nucleotide phosphodiesterases (cPDE) and some patho-biologic behaviors of stomach cancer--I. Histochemical studies of CPDE in stomach cancer tissues]. 255 63

We tested the truncated 7-37 glucagon-like peptide 1 (TGLP-1), a naturally occurring porcine intestinal peptide, and other members of the glucagon family, including pancreatic glucagon (G-29), GLP-1 and GLP-2 for their ability to activate the cAMP generating system in rat gastric glands and HGT-1 human gastric cancer cells. In rat fundic glands, TGLP-1 was about 100 times more potent (EC50 = 2.8 X 10(-9) M) than GLP-1 of G-29, and 10 times more potent than G-29 in the HGT-1 cell line. Our results support the notion that TGLP-1 plays a direct role in the regulation of acid secretion in rat and human gastric mucosa.
 ...
PMID:Effect of truncated glucagon-like peptide 1 on cAMP in rat gastric glands and HGT-1 human gastric cancer cells. 284 Nov 60

Pepsin is a potent proteolytic enzyme stored and secreted by chief cells in an inactive precursor form, pepsinogen. Its secretion is modulated by both cAMP and calcium-dependent mechanisms. Abnormalities in levels of pepsinogen and its various isozymogens have been linked clinically, epidemiologically, and experimentally to peptic ulcer disease and gastric carcinoma. The ulcerogenesis of pepsin stems from its ability to breach gastroduodenal mucosal barriers. Furthermore, certain isozymogens seems abundant and hyperactive in patients with peptic ulcer disease. The etiology and significance of low pepsinogen levels with disproportionate elevations of pepsinogen II and pepsin 5 in gastric cancer and its precursors is less clear. Further exploration of the patho-physiologic role of pepsin is likely to be of considerable importance in initiating further advances in the understanding and treatment of upper gastrointestinal disease.
 ...
PMID:Pepsinogen. Prolate ellipsoid or unrecognized pathogen? 330 25

In human fundic glands, famotidine was about 17 times more potent than ranitidine as an inhibitor of histamine - stimulated cAMP generation. This H2-receptor antagonist had no effect on the receptor-adenylate cyclase systems sensitive to PGE2, isoproterenol (beta 2-receptor), VIP and on forskolin-induced activation of the Gs/catalytic units of the membrane-bound enzyme prepared from human fundic glands. In the HGT-1 human gastric cancer cell line, famotidine and ranitidine showed long lasting, irreversible actions probably related to a slow rate of dissociation from the histamine H2-receptor.
 ...
PMID:Pharmacological control of the histamine H2 receptor-adenylate cyclase system by famotidine and ranitidine in normal and cancerous human gastric epithelia. 339 79

We compared the interaction of AH 22216 (a new histamine H2 receptor antagonist) and cimetidine on the receptor-cAMP systems sensitive to histamine and to Vasoactive Intestinal Peptide (VIP) in the human gastric cancer cell line HGT-1. When added simultaneously with histamine (10(-4) M), the potency of AH 22216 is similar to that of cimetidine (IC50 = 4-6.6 X 10(-6) M, respectively). Schild plot analysis indicated a non-competitive inhibition by AH 22216 (pA2 = 6.22, slope = 1.4 +/- 0.03). Preincubations of AH 22216 (10 min, 10(-5) M) with HGT-1 cells (even after a washout period) resulted in a complete and persistent (60 min) inactivation of the subsequent histamine effect, without changing the kinetics of the VIP-induced stimulation in the system. Under these conditions, the potency of AH 22216 increased from 6.6 to 0.7 X 10(-6) M. This inactivation was not observed with cimetidine. The data indicate that AH 22216 is an irreversible and specific inhibitor of the gastric histamine H2 receptor.
 ...
PMID:Irreversible and specific inactivation by AH 22216 of histamine H2 receptors in the human gastric cancer cell line HGT-1. 631 3

In the human gastric adenocarcinoma cell line AGS the effects of the protein-kinase-C-activating phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), the protein kinase C inhibitor staurosporine, the adenylate-cyclase activating agent forskolin, and the permeable dibutyryl-adenosine 3',5'-monophosphate (Bt2cAMP) on the proliferation were assessed. Cell counting followed 5 days of incubation. Prolonged activation of protein kinase C by TPA, inhibition of protein kinase C by staurosporine, activation of adenylate cyclase by forskolin or a direct increase of the intracellular cAMP level all result in a dose-dependent growth inhibition of AGS gastric tumour cells. Half-maximal inhibition was achieved at 100 pM for TPA, 1 nM for staurosporine, 20 microM for forskolin, and 600 microM for Bt2cAMP. It is concluded that protein kinase C and adenylate cyclase play a fundamental role in the growth of AGS gastric cancer cells. Interference with these enzymes involved in the signal transduction of growth regulation in tumour cells may represent a target in the development of new antiproliferative principles.
 ...
PMID:Protein kinase C and adenylate cyclase as targets for growth inhibition of human gastric cancer cells. 840 80

Eighty-eight gastropathic patients with Spleen deficiency syndrome by using transmission electron microscope (TEM), X-ray energy disperse analysis system (EDAX), histochemical staining and radioimmuno methods were examined. The authors found that the gastric mucosa cAMP, SOD level, the quantity of mitochondria and its crista, the ratio of diameter between ventricle and cavity of mitochondria and the content of Zn, Cu of mitochondria were reduced in the trend of healthy control group, Spleen Qi deficiency group, Spleen deficiency with Qi stagnation group; chronic superficial gastritis group, chronic atrophic gastritis group, gastric cancer group: complete small intestinal metaplasia group, incomplete small intestinal metaplasia group, complete colonic intestinal metaplasia group, incomplete colonic intestinal metaplasia group (P < 0.05-0.001). While the degeneration rate of mitochondria, the Cu/Zn ratio of mitochondria, the metaplasia rate of gastric, the rate of incomplete colonic intestinal metaplasia and the content of serum LPO were increased in the above turn. It is suggested that the comprehensive effect of the degeneration of mitochondria and the quantitative changes of its correlative factors is the physiopathologic base for inducing Spleen deficiency disease, gastric mucosa metaplasia and canceration. Much attention must be paid in clinic to the cancerization trend of gastric disease with Spleen deficiency syndrome.
 ...
PMID:[Study on mitochondrial ultrastructure, trace elements and correlative factors of gastric mucosa in patients with spleen deficiency syndrome]. 873 38

Gastric carcinoma is the second most common cause of cancer-related death worldwide. Recently, we have demonstrated that expressed sequence tag AA552509 was frequently amplified and the most consistently overexpressed target at 17q in gastric cancers. Herein, we report that DARPP-32 (dopamine and cAMP-regulated phosphoprotein of M(r) 32,000) is the target gene for overexpression of expressed sequence tag AA552509. In addition, we have identified full-length cDNA of DARPP-32 (GenBank accession number AF464196) with 467 bp of additional untranslated mRNA nucleotides upstream of the previously known translation start site in exon 1. Additionally, we have discovered a novel truncated isoform of DARPP-32 that we named t-DARPP (GenBank accession number AY070271), which is also overexpressed in gastric cancers. Using quantitative real-time reverse transcription-PCR, Western blots, and staining of tumor tissue arrays, the two DARPP mRNA transcripts and proteins were overexpressed in gastric cancer cells and exhibited abundant protein overexpression in neoplastic but not normal gastric epithelial cells. DARPP-32 is the only known protein that acts as a protein phosphatase 1 inhibitor or a protein kinase A inhibitor. The novel truncated isoform, t-DARPP, lacks the phosphorylation site related to protein phosphatase 1 inhibition but maintains the phosphorylation site with the protein kinase A inhibitory effect. Our results reveal for the first time the presence of these signaling molecules in human cancer and suggest that they may be important for gastric tumorigenesis.
 ...
PMID:Gastric cancers overexpress DARPP-32 and a novel isoform, t-DARPP. 1212 42

Splice variants (SVs) of receptors for growth hormone-releasing hormone (GHRH) have been found in primary human prostate cancers and diverse human cancer cell lines. GHRH antagonists inhibit growth of various experimental human cancers, including pancreatic and colorectal, xenografted into nude mice or cultured in vitro, and their antiproliferative action could be mediated in part through SVs of GHRH receptors. In this study we examined the expression of mRNA for GHRH and for SVs of its receptors in tumors of human pancreatic, colorectal, and gastric cancer cell lines grown in nude mice. mRNA for both GHRH and SV(1) isoform of GHRH receptors was expressed in tumors of pancreatic (SW1990, PANC-1, MIA PaCa-2, Capan-1, Capan-2, and CFPAC1), colonic (COLO 320DM and HT-29), and gastric (NCI-N87, HS746T, and AGS) cancer cell lines; mRNA for SV(2) was also present in Capan-1, Capan-2, CFPAC1, HT-29, and NCI-N87 tumors. In proliferation studies in vitro, the growth of pancreatic, colonic, and gastric cancer cells was stimulated by GHRH(1-29)NH(2) and inhibited by GHRH antagonist JV-1-38. The stimulation of some gastroenteropancreatic cancer cells by GHRH was followed by an increase in cAMP production, and GHRH antagonist JV-1-38 competitively inhibited this effect. Our study indicates the presence of an autocrine/paracrine stimulatory loop based on GHRH and SV(1) of GHRH receptors in human pancreatic, colorectal, and gastric cancers. The finding of SV(1) receptor in human cancers provides an approach to an antitumor therapy based on the blockade of this receptor by specific GHRH antagonists.
 ...
PMID:The expression of growth hormone-releasing hormone (GHRH) and splice variants of its receptor in human gastroenteropancreatic carcinomas. 1218 80


1 2 3 Next >>